Abstract
During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-κB) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-κB activation has been intensively studied, ligand-independent NF-κB activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-κB activation, whereby Nkx3.2 recruits the RelA-IκBα heteromeric complex into the nucleus by direct protein-protein interactions and activates RelA through proteasome-dependent IκBα degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-κB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.
| Original language | English |
|---|---|
| Pages (from-to) | 287-298 |
| Number of pages | 12 |
| Journal | Nature Cell Biology |
| Volume | 9 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2007 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability. / Park, Minsun; Yong, Yeryoung; Choi, Seung Won; Kim, Jae Hwan; Lee, Jong Eun; Kim, Dae Won.
In: Nature Cell Biology, Vol. 9, No. 3, 01.03.2007, p. 287-298.Research output: Contribution to journal › Article
TY - JOUR
T1 - Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability
AU - Park, Minsun
AU - Yong, Yeryoung
AU - Choi, Seung Won
AU - Kim, Jae Hwan
AU - Lee, Jong Eun
AU - Kim, Dae Won
PY - 2007/3/1
Y1 - 2007/3/1
N2 - During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-κB) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-κB activation has been intensively studied, ligand-independent NF-κB activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-κB activation, whereby Nkx3.2 recruits the RelA-IκBα heteromeric complex into the nucleus by direct protein-protein interactions and activates RelA through proteasome-dependent IκBα degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-κB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.
AB - During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-κB) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-κB activation has been intensively studied, ligand-independent NF-κB activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-κB activation, whereby Nkx3.2 recruits the RelA-IκBα heteromeric complex into the nucleus by direct protein-protein interactions and activates RelA through proteasome-dependent IκBα degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-κB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.
UR - http://www.scopus.com/inward/record.url?scp=33847360487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847360487&partnerID=8YFLogxK
U2 - 10.1038/ncb1538
DO - 10.1038/ncb1538
M3 - Article
C2 - 17310243
AN - SCOPUS:33847360487
VL - 9
SP - 287
EP - 298
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 3
ER -